Microneedle patch applicator and housing for same

ABSTRACT

A microneedle patch applicator housing, being formed from a single sheet or film having a top surface and an undersurface, the housing including a flat peripheral base part and a raised part surround by the peripheral base part and bulging vertically, with respect to the peripheral base part, from the undersurface toward the top surface, an undersurface portion of the raised part forming a surface supporting a microneedle patch, the raised part including a plurality of concavely bent parts, and the concavely bent parts each having a concave bottom toward a direction away from a center portion of the raised part.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. Ser. No. 16/062,671,filed on Jun. 15, 2018, which is a national stage application ofPCT/JP2016/087965, filed in Japan on Dec. 20, 2016, and which claims thepriority of PCT/JP2015/085707, filed in Japan on Dec. 21, 2015 and JP2016-158930, filed in Japan on Aug. 12, 2016. The subject matter of USSer. No. 16/062,671; PCT/JP2016/087965; PCT/JP2015/085707; and JP2016-158930 is incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a microneedle patch applicator thatapplies a microneedle patch to skin of animals (including human beingsand animals other than human beings). The present invention relates alsoto a microneedle patch applicator housing.

BACKGROUND ART

Recent attention has been given to a drug administration system using adrug-coated microneedle patch as one of percutaneously absorbed drugadministration systems (see Patent Documents 1 to 7). This microneedlepatch has, on its base material, densely formed thin protuberances orneedles of several hundred microns in length. The needles carryingtarget drug (vaccine, protein, or molecules such as peptide) thereon ortherein are stuck into skin to directly transport the drug to dermis orepidermis. The microneedle patch has a number of advantages such as notimposing a burden on the liver unlike oral medicines, not inducing apain by penetration of the needle unlike injections, and being able toreduce side effects caused by transient excess absorption of drug.

The needles of the microneedle patch are each extremely thin (approx.several tens of microns in root diameter). Therefore, the needles maypossibly be damaged or broken by the resistance upon penetration intoskin. In the case of needles made of a metal (e.g. titanium), indwellingrisk arising from intracutaneous breakage is a significant problem.Needles made of a biodegradable resin may be damaged or broken moreeasily than the metal needles. In particular, if the needles are tiltedwith respect to skin, insertability of needles into skin lowers or theneedles become easy to break due to a bending force acting thereon.Thus, there is a need for means enabling the needles to be puncturedvertical to skin and ensuring secure application of the microneedlepatch to skin.

PRIOR ART DOCUMENT Patent Document

-   Patent Document 1: JP-A-2006-149818-   Patent Document 2: JP-T-2008-520369-   Patent Document 3: JP-T-2008-543528-   Patent Document 4: JP-T-2008-535587-   Patent Document 5: JP-T-2010-516337-   Patent Document 6: JP-Re-2009-107806-   Patent Document 7: JP-Re-2011-089907

SUMMARY OF THE INVENTION Problem to be Solved by the Invention

The present invention provides a microneedle patch applicator and amicroneedle patch applicator housing, capable of enhancing the verticalpenetration properties of needles relative to skin and ensuring secureapplication of a microneedle patch onto skin.

Means for Solving Problem

In an embodiment of a microneedle patch applicator housing according tothe present invention,

the housing is formed from a single sheet or film having a top surfaceand an undersurface and comprises a flat peripheral base part and araised part surround by the peripheral base part and bulging vertically,with respect to the peripheral base part, from the undersurface towardthe top surface,

an undersurface portion of the raised part forms a surface supporting amicroneedle patch,

the raised part includes a plurality of concavely bent parts, and

the concavely bent parts each have a concave bottom toward a directionaway from a center portion of the raised part.

In another embodiment of the microneedle patch applicator housing, theconcavely bent parts are arranged symmetrically with respect to twohorizontal axes (x-axis and y-axis) that are orthogonal to a verticalaxis (z-axis) extending through a center of the raised part and that areorthogonal to each other.

In another embodiment of the microneedle patch applicator housing, theconcavely bent parts are arranged with a rotational symmetry (n-foldsymmetry: n is an integer greater than or equal to 2).

In another embodiment of the microneedle patch applicator housing, theraised part is shaped symmetrical with respect to at least one of thetwo horizontal axes (x-axis and y-axis).

In another embodiment of the microneedle patch applicator housing, theraised part is shaped symmetrical with respect to the two horizontalaxes (x-axis and y-axis).

In another embodiment of the microneedle patch applicator housing, theraised part is shaped with a long axis (x-axis) that is one of the twohorizontal axes (x-axis and y-axis) and with a short axis (y-axis) thatis the other of the two horizontal axes.

In another embodiment of the microneedle patch applicator housing, theraised part is rotationally symmetrical (n-fold symmetry: n is aninteger greater than or equal to 2) with respect to a vertical axis(z-axis) extending through a center of the raised part.

In another embodiment of the microneedle patch applicator housing, theraised part has at a center a recess, an undersurface portion of whichforms a surface supporting the microneedle patch.

In another embodiment of the microneedle patch applicator housing, itcomprises a ridge extending along a contour of the raised part andsurrounding the recess, the ridge including a plurality of concavelybent parts.

In another embodiment of the microneedle patch applicator housing, thecontour is shaped symmetrical with respect to the two horizontal axes(x-axis and y-axis).

In another embodiment of the microneedle patch applicator housing, thecontour is shaped with a long axis (x-axis) that is one of the twohorizontal axes (x-axis and y-axis) and with a short axis (y-axis) thatis the other of the two horizontal axes.

In another embodiment of the microneedle patch applicator housing, thecontour is rotationally symmetrical (n-fold symmetry: n is an integergreater than or equal to 2) with respect to the vertical axis (z-axis).

In another embodiment of the microneedle patch applicator housing, therecess includes a flat surface, the flat surface having twoeasy-to-deform parts that are arranged symmetrically with respect to theshort axis and that extend parallel to the short axis (y-axis), the flatsurface including a center region interposed between the twoeasy-to-deform parts and end regions positioned on both sides of thecenter region.

In another embodiment of the microneedle patch applicator housing, theraised part is disposed continuously circumferentially around thevertical axis (z-axis).

In another embodiment of the microneedle patch applicator housing, theraised part is disposed discontinuously circumferentially around thevertical axis.

In another embodiment of the microneedle patch applicator housing, atleast one or more of the plurality of concavely bent parts have aconcave bottom sloped downward toward a direction away from a centerportion of the raised part.

An embodiment of a microneedle patch applicator according to the presentinvention comprises:

the microneedle patch applicator housing of any one of the above; and

a microneedle patch supported on a surface that supports the microneedlepatch.

In another embodiment of the microneedle patch applicator, the recesscomprises a finger hold.

In an embodiment of the microneedle patch applicator,

a protective sheet is affixed to an undersurface of the housing,

the protective sheet closing an opening of a microneedle patch storagespace formed at the back of the raised part.

In another embodiment of the microneedle patch applicator,

the finger hold comprises an indicator indicating that a predeterminedforce is applied to the finger hold.

Effect of the Invention

According to the microneedle patch applicator and the housing for thesame in accordance with the present invention, when the raised part ispressed, the patch carried on the back surface thereof deformsvertically and deeply relative to skin. As a result, the entirety of thepatch is vertically pressed against skin with a uniform force. Thisallows the needles disposed on the patch to penetrate vertically intoskin so that the needles cannot be bend, damaged, or broken at the timeof puncture.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view, from diagonally above, of a microneedlepatch applicator and a housing for the same according to a firstembodiment.

FIG. 2 is a perspective view, from diagonally below, of the microneedlepatch applicator and the housing for the same shown in FIG. 1 .

FIG. 3 is a perspective view, from diagonally above, of the microneedlepatch applicator having a finger hold and the housing for the same.

FIG. 4A is a perspective view of the finger hold.

FIG. 4B is a plan view of the finger hold.

FIG. 4C is a front view of the finger hold.

FIG. 5 is a perspective view, from diagonally below, of the microneedlepatch applicator having a microneedle chip and the housing for the same.

FIG. 6 is a schematic enlarged sectional view of a microneedle patch.

FIG. 7 is a perspective view of a deformation preventing member fittedto a patch storage space of the microneedle patch applicator housingshown in FIG. 1 .

FIG. 8 is a perspective view, from diagonally above, of a microneedlepatch applicator and a housing for the same according to a secondembodiment.

FIG. 9 is a perspective view, from diagonally above, of a microneedlepatch applicator housing according to a third embodiment.

FIG. 10 is a perspective view, from diagonally above, of a microneedlepatch applicator and a housing for the same according to a fourthembodiment.

FIG. 11 is a perspective view, from diagonally above, of the housingshown in FIG. 10 .

FIG. 12 is a perspective view, from diagonally below, of the housingshown in FIG. 10 .

FIG. 13 is a perspective view, from diagonally below, of the housing ofFIG. 10 to which the microneedle patch is attached.

FIG. 14 is a perspective view, from diagonally below, of the housing ofFIG. 10 having a bottom to which a protective seal is affixed.

FIG. 15 is a perspective view of a deformation preventing member fittedto the housing shown in FIG. 10 .

FIG. 16A is an upper perspective view of a microneedle patch applicatorand a housing for the same according to a fifth embodiment.

FIG. 16B is a lower perspective view of the microneedle patch applicatorand the housing for the same according to a fifth embodiment.

FIG. 17A is an upper perspective view of a microneedle patch applicatorand a housing for the same according to a sixth embodiment.

FIG. 17B is a lower perspective view of the microneedle patch applicatorand the housing for the same according to a sixth embodiment.

FIG. 18 is a perspective view, from diagonally above, of a microneedlepatch applicator and a housing for the same according to a seventhembodiment.

FIG. 19A is an upper perspective view of a microneedle patch applicatorand a housing for the same according to an eighth embodiment.

FIG. 19B is a lower perspective view, from diagonally above, of themicroneedle patch applicator and the housing for the same according toan eighth embodiment.

FIG. 20 is an exploded perspective view showing a finger hold of anothermode.

FIG. 21 is a perspective view of a microneedle patch applicatoraccording to a ninth embodiment.

FIG. 22 is a partially exploded perspective view of the microneedlepatch applicator according to the ninth embodiment shown in FIG. 21 .

FIG. 23A is an exploded perspective view (FIG. 23(A)) of the microneedlepatch applicator according to the ninth embodiment shown in FIG. 21 .

FIG. 23B is a front view of a torsion spring assembled in themicroneedle patch applicator shown in FIG. 23A.

FIG. 24A is a lower, exploded perspective view of a lower structureassembled in the microneedle patch applicator according to the ninthembodiment of FIG. 21 .

FIG. 24B is an upper perspective view of the lower structure inperspective view.

FIG. 24C is a bottom view of the lower structure.

FIG. 25A is an upper, exploded perspective view of a microneedle patchapplicator according to a tenth embodiment.

FIG. 25B is an exploded front view of the microneedle patch applicatoraccording to a tenth embodiment.

FIG. 26 is a perspective view of a microneedle patch applicatoraccording to an eleventh embodiment.

FIG. 27 is an exploded perspective view of the microneedle patchapplicator according to the eleventh embodiment shown in FIG. 26 .

FIG. 28 is a perspective view of a microneedle patch applicator ofanother mode.

FIG. 29 is a partially exploded perspective view of the microneedlepatch applicator shown in FIG. 28 .

MODES FOR CARRYING OUT THE INVENTION

Embodiments of a microneedle patch applicator and a microneedle patchapplicator housing according to the present invention will now bedescribed with reference to the accompanying drawings.

First Embodiment

FIG. 1 shows a microneedle patch applicator (hereinafter, referred to as“applicator”) 1 according to a first embodiment.

The applicator 1 comprises a container or housing 11 that houses amicroneedle patch 40 (see FIG. 6 ) that will be described later.

The housing 11 is formed (e.g. vacuum forming, pressure forming, orpress forming) for example from a thin resin sheet or film or molded(e.g. injection molding) from a molten resin injected into a cavity of amold and has an external shape shown. A material suitable for forming ormolding of the housing is desirably a material having a flexibility andeasy to be bent, deformed or restored and can be for example a resinsuch as polyethylene, polypropylene, polyethylene terephthalate,polystyrene, nylon, acrylic, silicone, or ABS resin. Unless the abovecharacteristics such as flexibility are impaired, these resins maycontain a hygroscopic agent and/or an oxygen absorber, etc. so as toimpart hygroscopic and/or oxygen absorbing functions thereto. Thethicknesses of parts of the housing are properly determined such that adesired deformation described later occurs when the housing 11 ispressed from above with a human finger. It is desirable that the housinghave a feature of easily bending at a concavely bent part that will bedescribed later. For example, in the case of the housing made ofpolyethylene, polypropylene, or polyethylene terephthalate, thethicknesses of parts are preferably approx. 50 μm to 1 mm, morepreferably 100 μm to 500 μm.

The housing 11 comprises a flat plate-like peripheral base part 12 and araised part 13 that is surround by the peripheral base part 12 and thatis raised upward (in z-axis direction of FIG. 1 ) from the peripheralbase part 12. The peripheral base part 12 is surrounded by asubstantially rectangular outer edge 14. The raised part 13 has asubstantially rectangular contour 15 that is substantially similar tothe rectangular outer edge 14 of the peripheral base part 12. In theembodiment, the contour 15 includes a pair of long-side-directioncontour parts 16 extending in the long-side direction (x-axis directionof FIG. 1 ) of the rectangular peripheral base part 12 and a pair ofshort-side-direction contour parts 17 extending in the short-sidedirection (y-axis direction of FIG. 1 ) thereof.

The raised part 13 has a substantially truncated pyramid shape andcomprises a long-side-direction side wall 18 and a short-side-directionside wall 19 which extend upward from the long-side-direction contourpart 16 and the short-side-direction contour part 17, respectively. Thelong-side-direction side wall 18 and the short-side-direction side wall19 may be tilted inward. A top of the raised part 13 includes along-side-direction tilted top-surface portion 22 and ashort-side-direction tilted top-surface portion 23 which extend from anupper end 20 of the long-side-direction side wall 18 and an upper end 21of the short-side-direction side wall 19, respectively, toward a centerof the raised part 13. Preferably, the long-side-direction tiltedtop-surface portion 22 and the short-side-direction tilted top-surfaceportion 23 are downward tilted inward from the upper end 20 and theupper end 21, respectively.

The long-side-direction tilted top-surface portion 22 and theshort-side-direction tilted top-surface portion 23 are in contact witheach other at a boundary extending in a direction which forms apredetermined angle (e.g. approx. 45 degrees) relative to the upper end20 of the long-side-direction side wall 18 and the upper end 21 of theshort-side-direction side wall 19, respectively, when the raised part 13is viewed from above. Since the long-side-direction tilted top-surfaceportion 22 and the short-side-direction tilted top-surface portion 23are each tilted diagonally downward toward the center of the raised part13 as described above, the boundary forms a concavely bent part 24. Thepart of the concavely bent part 24 may be thinner than the right andleft regions (the top-surface portions 22 and 23) or may have a U-shapedor inverted U-shaped section.

The raised part 13 has a recess 25 at the center thereof. The recess 25includes a circumferential wall 26 extending downward from inner edgesof the long-side-direction tilted top-surface portion 22 and theshort-side-direction tilted top-surface portion 23 and a substantiallyflat bottom 27 connected to a lower end of the circumferential wall 26.

As shown, the recess 25 is in the shape of a track when viewed fromabove. The bottom 27 of the recess 25 includes two easy-to-deform parts28 extending in the short-side direction. As shown, the easy-to-deformparts 28 are arranged symmetrically with respect to a center (anintersection of X-axis, Y-axis, and Z-axis shown) of the recess 25 sothat end regions 30 on both sides of a center region 29 interposedbetween the two easy-to-deform parts 28 can easily bend upward from thecenter region 29. The easy-to-deform part 28 may be in the form of athinned portion that is thinner than the other portions or a deformedportion having a section bent into U shape or inverted-U shape.

In the embodiment, as shown in FIG. 3 , the recess 25 of the raised part13 may comprise a finger hold (a pressed portion) 31 against which theuser presses his/her finger upon operation. The finger hold 31 has acontour substantially equal to or slightly smaller than the contour ofthe recess 25.

As shown in FIG. 4 , the finger hold 31 comprises an upper member 32 anda lower member 33. When viewed from above, the upper member 32 has theshape of a track substantially equal in size to the recess 25. The lowermember 33 has, at both ends in the longitudinal direction (near anarcuate portion), a support 34 protruding upward from the top of thelower member 33. The lower member 33 has, at its center, a boss(protrusion) 35 protruding upward from the top thereof. In theembodiment, the boss 35 is of a cylindrical shape. A bottom of the lowermember 33 is a slant surface that includes end regions 36 extendingdiagonally upward from edges of a center region 37. Accordingly, whenthe finger hold 31 is stored in the recess 25, only the center region 37of the lower member 33 is in contact with the center region 29 of therecess bottom 27, with the end regions 36 of the lower member 33 beingspaced apart from the end regions 30 of the recess bottom 27.

Corresponding to the support 34 of the lower member 33, the upper member32 comprises a pair of protuberances 38 protruding downward from thebottom of the upper member 32. The position pf the protuberance 38 isdetermined such that the upper member 32 is positioned with respect tothe lower member 33 so that an inner edge of the protuberance 38 lies atan outer edge of the support 34 when the upper member 32 is assembled onthe lower member 33. The upper member 32 has at its center athrough-hole 39 extending vertically. It is preferred that thecross-section of the through-hole 39 be greater than or slightly greaterthan the cross-section of the boss 35 of the lower member 33. Theposition of the through-hole 39 is determined such that, when the uppermember 32 is assembled on the lower member 33, the boss 35 and thethrough-hole 39 are coaxial and vertically confront each other.

Various conditions of the upper member 32 and the lower member 33 (e.g.materials making up the upper material 32 and the lower material 33, thethicknesses thereof, and the height of the boss 35) are determined suchthat, when a finger is abutted against the top of the upper member 32 toapply a predetermined pressing force (that will be described later)thereto, the upper member 32 flexes at its center portion downward withrespect to the both-side portions thereof, or that the lower member 33flexes at its center portion relatively upward with respect to theboth-side portions thereof, or that the upper member 32 and the lowermember 33 flexes at their respective center portions downward andupward, respectively, so that the boss 35 passes through thethrough-hole 39 of the upper member 32 to protrude from its top by apredetermined length to abut against the finger. It is thereforepreferred that elastic materials allowing such deformations be selectedas the materials of the upper member 32 and the lower member 33.

The thus configured finger hold 31 is disposed in the recess 25, withthe upper material 32 and the lower material 33 combined. The combinedupper member 32 and lower member 33 may be adhered to each other by anadhesive or may be integrally molded. The center region 37 of the lowermember undersurface and the recess bottom center region 29 confrontingthe center region 37 may be adhered to each other by an adhesive or adouble-sided tape. The finger hold 31 need not be mounted in advance onthe housing 11 and the finger hold 31 may be mounted in advance in therecess 25 before use of the applicator 1.

As shown in FIG. 5 , a microneedle patch (hereinafter, referred to as“patch”) 40 is stored in a patch storage space 41 formed on the backsurface of the raised part 13 and is secured to a patch support surface42 configured by the back surface of the recess 25.

In general, as shown in FIG. 6 , the patch 40 comprises a sheetsubstrate 43 and a microneedle array 44 supported thereby. The sheetsubstrate 43 includes a substrate film 45, a pressure-sensitive adhesivelayer 46 disposed on an undersurface of the substrate film 45 (a supportsurface of the microneedle array 44), and a release treatment layer (arelease layer) 47 disposed on a top surface of the substrate film 45 (asurface confronting the patch support surface 42). The microneedle array44 includes a quadrangular (or circular) base layer 48 and amultiplicity of elongated needles 49 of a predetermined height (e.g. 300to 1000 micrometer) arranged regularly at predetermined intervals (e.g.300 to 1000 micrometer) in lattice or in honeycomb on an undersurface ofthe base layer 48. The microneedle array 44 is made by filling, forexample, a biodegradable synthetic polymer material (e.g. hyaluronicacid, collagen, polylactic acid, or polyglycolic acid) into a mold of acorresponding shape. Although not shown, the needle 49 is coated at itstip side with a target drug (vaccine, protein, or molecules such aspeptide). Alternatively or additionally, in the case of making themicroneedle array 44 of a biodegradable resin, the target drug may becontained in the interior of the needle 49 upon molding thereof.

The sheet substrate 43 and the microneedle array 44 are integrated byadhering the base layer 48 of the microneedle array 44 onto thepressure-sensitive adhesive layer 46 of the sheet substrate 43. As shownin FIGS. 5 and 6 , the sheet substrate 43 is larger than the microneedlearray 44. Accordingly, when the microneedle array 44 is adhered to thesheet substrate 43, a sufficient area of pressure-sensitive adhesivelayer 46 is exposed around the microneedle array 44.

The thus formed patch 40 is adhered to the patch support surface 42 byuse of a double-sided tape 50. When adhered, the microneedle array 44lies in the patch support surface center region 37 corresponding to therecess center region 29 while the double-sided tapes 50 on both sideslies in the patch support surface end regions 36 corresponding to therecess end regions 30.

The double-sided tape 50 serves to temporarily hold the patch 40 on thepatch support surface 42 prior to adhesion of the patch 40 onto skin.After adhesion of the patch 40 onto skin, the patch 40 need to be heldon skin, apart from the housing 11. It is therefore preferred thatconditions (size, shape, attachment position, adhesive force) of thedouble-sided tape 50 be determined such that the adhesive force of thedouble-sided tape 50 to the release treatment layer (release layer) 47be less than the adhesive force of the pressure-sensitive adhesive layer46 to skin. Specifically, as shown, the double-sided tape 50 ispreferably attached to positions displaced inward by a predetermineddistance (designated at reference numeral 51 in FIG. 6 ) from both endsof the sheet substrate 43 so that, when removing the housing 11 fromskin after adhesion of the patch 40, the double-sided tape 50 can bereleased gradually from the release treatment layer 47, inwardly fromthe outer edges 50 a. The double-sided tape 50 may be replaced by anadhesive.

In order to protect the patch 40 stored in the patch storage space 41,as shown by a broken line in FIG. 2 , a protective sheet 55 of a sizeenough to close the opening of the patch storage space 41 is preferablyattached to the undersurface of the housing 1. It is preferred that thesize of the protective sheet 55 be substantially equal to the contour ofthe housing 11. Preferably, the protective sheet 55 includes a tab 55 acaught by the user when the protective sheet 55 is released from thehousing 11. The patch storage space 41 may hermetically contain, in itsinterior, agents such as a moisture absorbent and an oxygen absorbentfor suppressing degradation of the microneedles and of drug carriedthereon.

Usage of the thus configured applicator 1 will be described.

The protective sheet 55 affixed to the bottom surface of the housing 11is first peeled off to expose the patch 40.

The applicator is then placed on skin such that the peripheral base part12 of the housing 11 abuts against skin.

Subsequently, a finger (a thumb for example) is abutted on the topsurface of the finger hold 31 to press the applicator 1 against skin.This allows the raised part 13 of the housing 11 made of a thin resinsheet or film to deform. At that time, the raised part 13 convexly bendsat the concavely bent parts 24, respectively, to displace the recess 25,the finger hold 31, and the patch 40 downward toward skin. Since thehousing 11 is formed from a thin sheet or film, the raised part 13easily deforms downward even with a small pressing force, allowing adownward displacement of the recess 25 with ease.

Thus, the patch 40 progresses toward skin with a small force. Aftercontact with skin, the patch 40 progresses vertically together with skinand, in its entirety, is pressed against skin with a uniform force.Since the needles 49 enter perpendicularly into skin, the needles 49 areprevented from bending, damaging, or breaking at the time of puncturing.

Next, when a predetermined pressing force is applied to the finger hold31, the upper member 32 deforms at its center portion downward by apredetermined amount with respect to the both sides thereof, or thelower member 33 deforms at its center portion upward by a predeterminedamount with respect to the both sides thereof, or the upper member 32and the lower member 33 deform at their respective center portionsdownward and upward, respectively, with the result that the boss 35passes through the through-hole 39 of the upper member 32 to protrude bya predetermined length from the top surface thereof, abutting on thefinger pressing the finger hold 31. As a result, the boss 35 functionsas an indicator so that the user can recognize that a required force isapplied to the finger hold 31. Application of the required force to thefinger hold 31 allows the needles 49 of the microneedle patch 40 toenter into skin by a predetermined amount. In consequence, the drugcarried on the needles 49 can securely be administered to skin.

With the predetermined pressing force being applied, the recess bottom27 of the raised part 13 bends at the easy-to-deform part 28 so that theundersurface center region 37 and the end regions of the finger holdlower member 33 come into contact with the center region 29 and the endregions (slant surface), respectively, of the recess 25, allowing themicroneedles 44 supported on the recess center region to be pressedagainst skin with a required force. As a result, a sufficientpressure-sensitive adhesive force (which is greater than thepressure-sensitive adhesive force of the double-sided tape 50 to therelease treatment layer (release layer) 47) is secured between the patch40 (particularly, pressure-sensitive adhesive layer 46) and skin.

When the force applied to the finger hold 31 is removed, the housing 11restores to its pre-deformation shape by its own elasticity, allowingthe end regions of the patch 40 adhered to skin to come apart from skin,starting from its edges. Since the undersurface center region 37 and endregions 36 of the finger hold lower member 33 are in contact with thecenter region 29 and end regions (slant surfaces) 30 of the recess 25,respectively, the ends of the patch 40 lie slant along the end regions36, with the result that the release force acts on the outer edges ofthe double-sided tape 50 in a concentrated manner. Consequently, withthe patch 40 being adhered to skin, the patch 40 is easily released fromthe double-sided tape 50 and separates from the housing 11.

As described above, the housing 11 of the applicator 1 is made of arelatively deformable material, and hence it is preferred to prevent theneedles 49 from coming into contact with the protective sheet 55 as aresult of pre-use deformation of the raised part 13. It is thereforepreferred as shown in FIG. 7 to prepare a deformation preventing member56 having an external shape complementary to the rear shape of theraised part 13 (i.e. the patch storage space 41) and to store thedeformation preventing member 56 into the patch storage space 41 beforeadhesion of the protective sheet 55 or before attachment of the patch40. For the purpose of preventing deformation, the external shape andmaterial of the deformation preventing member 56 are determined so as toprevent the needles from coming into contact with the protective sheetas a result of a large deformation of the housing 11 even when thehousing is subjected to a predetermined force. For the purpose ofprotecting the needles, the shape of a portion of the deformationpreventing member 56 confronting the patch is preferably determined suchthat a space of predetermined dimensions is formed between thedeformation preventing member 56 and the patch. Although the deformationpreventing member 56 of this embodiment shown in FIG. 7 has acomplementary shape to that of the patch storage space 41, thedeformation preventing material may employ any shape as long as theabove purposes can be achieved.

Instead of the deformation preventing member 56 or in addition to thedeformation preventing member 56, the patch storage space 41 may behermetically sealed by a protective sheet. The patch storage space maybe filled with an inert gas such as nitrogen or a dry gas to replace airtherewith. In this case, due to the existence of air or a replacementgas within the hermetically sealed patch storage space, the housing canretain its shape even when it is subjected to an external force,preventing the microneedles from coming into contact with the sheet. Acompressed gas may be hermetically enclosed for shape retaining.

Second Embodiment

FIG. 8 shows a housing 111 of an applicator of a second embodiment.Similar to the first embodiment, the housing 111 is formed (e.g. vacuumforming, pressure forming, or press forming) for example from a thinresin sheet or film or molded (e.g. injection molding) from a moltenresin injected into a cavity of a mold. A material suitable for formingor molding of the housing is desirably a material having a flexibilityand easy to be bent, deformed or restored and can be for example a resinsuch as polyethylene, polypropylene, polyethylene terephthalate,polystyrene, nylon, acrylic, silicone, or ABS resin. The thicknesses ofparts of the housing are properly determined such that a desireddeformation described later occurs when the housing 111 is pressed fromabove with a human finger. For example, in the case of the housing madeof polyethylene, polypropylene, or polyethylene terephthalate, thethicknesses of parts are preferably approx. 50 μm to 1 mm, morepreferably 100 μm to 500 μm.

The housing 111 comprises a flat plate-like peripheral base part 112 anda raised part 113 that is surround by the peripheral base part 112 andraised upward from the peripheral base part 112. The peripheral basepart 112 is surrounded by a substantially rectangular outer edge 114.The raised part 113 has a substantially rectangular contour 115 that issubstantially similar to the rectangular outer edge 114 of theperipheral base part 112. In the embodiment, the contour 115 includes apair of long-side-direction contour parts 116 extending in the long-sidedirection of the rectangular peripheral base part 112 and a pair ofshort-side-direction contour parts 117 extending in the short-sidedirection thereof.

The raised part 113 has a substantially truncated pyramid shape andcomprises a long-side-direction side wall 118 and a short-side-directionside wall 119 which extend upward from the long-side-direction contourpart 116 and the short-side-direction contour part 117, respectively.The long-side-direction side wall 118 and the short-side-direction sidewall 119 may be tilted inward. In the second embodiment, the side walls118 and 119 each include a lower-stage tilted side wall portion that isslightly tilted and an upper-stage tilted side wall portion that istilted at a greater tilt angle than that of the lower-stage tilted sidewall portion.

A top surface 123 of the raised part 113 includes a peripheral region125 and a rectangular or track-shaped recess (center region) 124surrounded by the peripheral region 125, that are bounded by an upperend 120 of the long-side-direction side wall 118 and an upper end 121 ofthe short-side-direction side wall 119. The peripheral region 125surrounding the center region 124 of the top surface 123 may be ahorizontal surface or a slant surface that is slanted upward ordownward, inwardly from the long-side-direction side wall upper end 120and the short-side-direction side wall upper end 121.

The raised part 113 has at its four corners concavely bent parts 126extending radially, when viewed from above, from the corners of theraised part 113 toward corners of the center region 124. In the secondembodiment, the concavely bent part 126 includes a concave bottom 127extending horizontally or diagonally upward from the vicinity of asubstantial boundary of the upper-stage tilted side wall portion and thelower-stage tilted side wall portion toward the edge of the centerregion 124.

According to the second embodiment, in the same manner as the firstembodiment, the microneedle patch is stored in the patch storage spaceformed on the back surface of the raised part 113 and is held on thepatch support surface that is the back surface of the center region 124.In order to protect the patch stored in the patch storage space, aprotective sheet of a size enough to close the opening of the patchstorage space may be affixed to the undersurface of the housing 1 (seeFIG. 2 ) and the protective sheet may have an easy peel feature so as toallow easy manual opening. Furthermore, the raised part 113 may have onits center region 124 the finger hold described in the first embodiment.

According to the applicator and housing of the second embodimentconfigured in this manner, when the applicator storing the patch isplaced on skin and the center region 124 of the housing or the fingerhold disposed thereon is pressed, the concavely bent part 126 isconcavely bent around the concave bottom 127, allowing the raised part113 of the housing to deform downward. At this time, since the housing111 is made of a thin sheet or film, the raised part 113 easily deformsdownward even with a small pressing force. The patch progressesperpendicularly more deeply toward skin with a small force and, in itsentirety, is pressed against skin with a uniform force. Since theneedles enter perpendicularly into skin, the needles are prevented frombending, damaging, or breaking at the time of puncturing.

In the second embodiment, similarly to the first embodiment, thedeformation preventing member may be disposed in the patch storagespace; the patch storage space may be hermetically sealed by theprotective sheet; and/or a compressed gas may be hermetically filled inthe patch storage space completely sealed by the protective sheet. Amoisture absorbent or an oxygen absorbent may be filled in the interiorof the housing; the housing itself may be made of a moisture absorbingmaterial; or it may be made of an oxygen absorbing material.

Third Embodiment

FIG. 9 shows a housing 211 of a third embodiment. The third embodimentis a variant of the second embodiment, in which a top surface centerregion 224 of a raised part 213 is planar without a recess. The otherconfigurations are the same as those of the second embodiment.

According to the third embodiment configured in this manner, similarlyto the first and second embodiments, when the applicator storing thepatch is placed on skin and a center region 224 of the housing or thefinger hold disposed thereon is pressed, a concavely bent part 226 isconcavely bent around a concave bottom 227, allowing a raised part 213of the housing to deform downward. At this time, since the housing ismade of a thin sheet or film, the raised part 213 easily deformsdownward even with a small pressing force. The patch progressesperpendicularly more deeply while pressing skin with a small force and,in its entirety, is pressed against skin with a uniform force. Since theneedles enter perpendicularly into skin, the needles are prevented frombending, damaging, or breaking at the time of puncturing.

Fourth Embodiment

FIG. 10 shows a microneedle patch applicator 300 according to a fourthembodiment, with FIGS. 11 and 12 showing a housing 301 for theapplicator.

The applicator 300 comprises the housing 301 holding a microneedle patch330 that will be described later.

The housing 301 is formed (e.g. vacuum forming, pressure forming, orpress forming) for example from a thin resin sheet or film or molded(e.g. injection molding) from a molten resin injected into a cavity of amold and has an external shape shown. Examples of a material suitablefor forming or molding of the housing include polyethylene,polypropylene, polyethylene terephthalate, polystyrene, nylon, acrylic,silicone, and ABS resins. The thicknesses of parts of the housing areproperly determined such that a desired deformation described lateroccurs when the housing 301 is pressed from above with a human finger.For example, in the case of the housing made of polyethylene,polypropylene, or polyethylene terephthalate, the thicknesses of partsare preferably approx. 50 μm to 1 mm, more preferably 100 μm to 500 μm.

The housing 301 comprises a flat plate-like peripheral base part 302 anda raised part 303 that is surround by the peripheral base part 302 andraised upward (in z-axis direction of FIG. 11 ) from the peripheral basepart 302. The peripheral base part 302 is surrounded by a substantiallyrectangular outer edge 304. The raised part 303 has a substantiallyoctagonal contour 305 when viewed from above. The contour 305 includes apair of long-side-direction contour parts 306 extending in the long-sidedirection (x-axis direction of FIG. 11 ) of the peripheral base part302, a pair of short-side-direction contour parts 307 extending in theshort-side direction (y-axis direction of FIG. 11 ) thereof, and fourdiagonal contour parts 308 each intersecting the long-side direction andthe short-side direction at a predetermined angle.

The raised part 303 comprises a caldera basin-like flat recess 310 at acenter thereof and a somma-like ridge 311 extending along the outercircumference of the recess 310 so as to encompass the recess 310. Thebottom of the recess 310 lies at a position enough higher than that ofthe peripheral base part 302 so that, when the housing 301 is placed onskin, a sufficient space is secured between skin and the back surface(which is a surface supporting the microneedle patch 330 (see FIG. 13 )as will be described later) of the recess 310.

The recess 310 has a track-shaped contour having a pair of parallellong-side-direction edges and substantially semi-arcuate edges joiningends thereof. In the embodiment, the recess 310 includes a pair ofeasy-to-deform parts 312 extending straight in the short-side direction,at positions apart a predetermined distance in the long-side direction(x-axis direction) from a center position (position at which x-axis andy-axis intersect) in the long-side direction. In this embodiment, theeasy-to-deform parts 312 are formed with their respective portions beingcurved upward so that end regions 314 lying on both sides of a centerregion 313 defined by the easy-to-deform parts 312 are easily bentupward relative to the center regions 313 around the easy-to-deformparts 312.

The ridge 311 includes a plurality of concavely bent parts radiallycrossing the ridge 311 from its inside to outside. In the embodiment,the ridge 311 includes 12 concavely bent parts 315, 316, and 317. The 12concavely bent parts 315, 316, and 317 are each formed symmetricallywith respect to a vertical axis (z-axis) extending through the center ofthe recess 310, a long axis (x-axis), and a short axis (y-axis). Forexample, at boundaries between each of the long-side-direction contourparts 306 and two diagonal contour parts 308 adjacent thereto, two firstconcavely bent parts 315 are radially arranged in such a manner that thedistance between the concavely bent parts increases gradually from theinside to the outside. At boundaries between each of theshort-side-direction contour parts 307 and two diagonal contour parts308 adjacent thereto, two second concavely bent parts 316 are radiallyarranged in such a manner that the distance between the concavely bentparts increases gradually from the inside to the outside. A single thirdconcavely bent part 317 is formed at the center of each of the diagonalcontour parts 308.

A concave bottom 318 of the first concavely bent part 315, a concavebottom 319 of the second concavely bent part 316, and a concave bottom320 of the third concavely bent part 317 are horizontal concave bottomsextending horizontally parallel to the peripheral base part 302 or areslant concave bottoms slanting toward the peripheral base part below.

Preferably, the concavely bent part is disposed at a plurality oflocations where a deformation may occur in a housing not having theconcavely bent part when a force is applied via a finger hold (pressedportion) 322 to the housing not having the concavely bent part. Thisallows even a weak force to deform the housing into a desired shape, sothat the housing can achieve a stable deformation.

The concavely bent part is preferably of a shape to facilitate thedeformation of the housing. It is therefore preferred to change theangle of the concave bottom, the shape, size, etc. of the concavely bentpart so as to fit the shape, etc. of the raised part. In consequence,the housing can be deformed into a desired shape even with a small forceand can achieve a stable deformation.

The housing 311 is formed by molding a thin sheet or film as describedabove and, at the back of the raised part 303, as shown in FIG. 12 ,comprises a microneedle patch storage space (recess) 321 of a shapecorresponding to that of the raised part 303. The recess 321 has on itsback surface a patch support surface 331. The patch support surface 331includes a center region 340 and end regions 341 corresponding to theback side of the center region 313 and the end regions 314 of the recess321. As shown in FIG. 13 , the patch 330 is disposed on the patchsupport surface 331, with a microneedle array 344 being supported on thecenter region 340, a double-sided tape 350 being carried on the both endregions 341. The double-sided tape 350 may be replaced by an adhesive.

Otherwise, configurations of the finger hold 322 (see FIG. 10 ), themicroneedle patch 330 (see FIG. 13 ), a protective sheet 355 (see FIG.14 ), and a deformation preventing member 356 (see FIG. 15 ) are thesame as in the first to third embodiments.

According to the applicator 300 and the housing 301 configured in thismanner, because the concave bottom 320 of the third concavely bent part317 extends diagonally downward from the inside toward the outside, theresistance force of the housing 301 against an inward deformation(which, at the same time, induces a vertical deformation toward thebase) of the raised part 303 becomes reduced. Hence, the raised part 303causes the patch 330 to advance vertically toward skin, while inwardlydeforming in such a manner that its entirety contracts. As a result, thepatch 330 advances vertically more deeply against skin with a smallforce and is, in its entirety, pressed against skin with a uniformforce. Since the needles enter vertically into skin, the needles cannotbe bent, damaged, or broken at the time of puncturing.

Fifth Embodiment

FIG. 16 shows a housing 501 of an applicator according to a fifthembodiment. In the housing 501, a raised part 503 is of a substantiallyoctagonal shape when viewed from above, with its contour 505 including along-side-direction contour part 506 extending in the long-sidedirection, a short-side-direction contour part 507 extending in theshort-side direction, and a diagonal contour part 508. A ridge 511 hasconcavely bent parts 515 and 516 formed at their respective locationscorresponding to boundaries of the long-side-direction contour part 506in the long-side direction, the short-side-direction contour part 507 inthe short-side direction, and the diagonal contour part 508. A concavebottom of the concavely bent part 515 is sloped downward toward theperipheral base part. A concave bottom of the concavely bent part 516may be sloped downward toward the peripheral base part or may behorizontal parallel to the peripheral base part.

In the fifth embodiment configured in this manner, because thedeformation is made allowing the concave bottom of the concavely bentpart 515 to be displaced in the inside direction orthogonal thereto, thevertical progression properties of the recess 510 and the patch can beenhanced. As a result, the patch advances vertically against skin with asmall force and is, in its entirety, pressed against skin with a uniformforce. Since the needles enter vertically into skin, the needles cannotbe bent, damaged, or broken at the time of puncturing.

Sixth Embodiment

FIG. 17 shows a housing 601 of an applicator according to a sixthembodiment. In the housing 601, a raised part 603 is of a substantiallyoctagonal shape when viewed from above, with its contour 605 including along-side-direction contour part 606 extending in the long-sidedirection, a short-side-direction contour part 607 extending in theshort-side direction, and a diagonal contour part 608, with concavelybent parts 615 and 616 being formed at boundaries of the adjacentcontour parts 605, 606, and 607. Concave bottoms of the concavely bentparts 615 and 616 are sloped downward from the inside toward theoutside.

In the sixth embodiment configured in this manner, directions ofdownward deformation of the concavely bent parts 615 and 616 having thesloped concave bottoms are symmetric with respect to a vertical planecontaining the long axis of the recess 610 and to a vertical planecontaining the short axis thereof and are directed diagonally inside,allowing the recess 610 and the patch carried on the back surfacethereof to advance vertically against the recess 610. As a result, thepatch advances vertically and more deeply against skin and is, in itsentirety, pressed against skin with a uniform force. Since the needlesenter vertically into skin, the needles cannot be bent, damaged, orbroken at the time of puncturing.

In this embodiment, the slope angle of the concave bottoms of theconcavely bent parts 615 lying on both sides of the long-side-directioncontour part 606 may be equal to the slope angle of the concave bottomsof the concavely bent parts 616 lying on both sides of theshort-side-direction contour part 607, or one may be greater than theother.

Seventh Embodiment

Although in the sixth embodiment the concave bottoms of all theconcavely bent parts are sloped downward from the inside of the raisedpart toward the outside thereof, the concave bottoms of all theconcavely bent parts 715 and 716 may be directed horizontally parallelto the peripheral base part as shown in FIG. 18 , or one of theconcavely bent parts 715 and 718 may be sloped with the other beingdirected horizontally.

Eighth Embodiment

Although in the above embodiments the raised part of the housing has apolygonal contour, a raised part 803 may have a circular contour asshown in FIG. 19 . In this embodiment, the raised part 803 of a housing801 may have a plurality of concavely bent parts 811 arrangedcircumferentially equiangularly and extending radially from the centerof a recess 810 or may have a plurality of concavely bent parts arrangedrotationally symmetrically on a vertical axis extending through thecenter of the raised part. It is preferred also in the housing of theeighth embodiment, similarly to the above embodiments, that the recess810 have at least two easy-to-deform parts 812 extending in parallel.

Variants

In the above embodiments, the planar shape of the housing raised part isnot limitative and may be a polygonal shape such as quadrangle,pentagon, and hexagon or may be a circle, ellipse, or a track shape. Itis preferred in all the modes the concavely bent part whose concavebottom is sloped and the concavely bent part having a sloped concavebottom are symmetrical with respect to a vertical plane containing thelong axis or the short axis of the raised part. In the case of polygonssuch as pentagon having an odd number of sides, the concavely bent partshaving a sloped concave bottom are preferably arranged circumferentiallyequiangularly around the vertical axis. Although in the case of thecircular raised part the long axis and the short axis cannot bedistinguished from each other, the concavely bent parts whose concavebottoms are sloped may be arranged symmetrically with respect to atleast one of two axes (orthogonal horizontal axes X and Y) orthogonal tothe center axis (Z-axis in the vertical direction) or may be arrangedcentrosymmetrically with respect to the center axis.

Similarly, the shapes of the recess and corresponding finger hold arenot limited to the track shape and may be any one of ellipse, circle,quadrangle, and the other polygons.

The ridge need not continuously be disposed around the recess and may bediscontinuous.

Although in the above description the patch is pressed via the fingerhold against skin, the recess may directly be pressed by a fingerwithout using the finger hold.

The raised part need not necessarily have the recess, and the top of theraised part may be a flat surface not having the recess. In this case,the concavely bent parts are formed on the outer periphery of the raisedpart. The number of the concavely bent parts and the slope angle of theconcave bottom are properly selected so as to ensure the needles'vertical puncturing properties.

The finger hold need not have the through-hole in its upper member,correspondingly to the boss on the lower member, and the upper member 32may have a thinned portion 851 at a location confronting the boss 35 onthe lower member 33 so that when a necessary force is applied to thefinger hold, the boss 35 deforms or breaks the thinned portion 851. Inthis case, the thinned portion 851 functions as an indicator informingthe operator that a predetermined pressing force has been applied to thefinger hold.

The indicator informing the operator that a predetermined pressing forcehas been applied to the finger hold may be configured for example suchthat when a predetermined pressing force is applied to the finger hold,specific feature portions formed on both the upper member and the lowermember come into contact with each other or move away from each other sothat the specific feature portion disposed on one of the upper memberand the lower member is broken to issue a sound (contact sound orbreakdown sound). Specifically, one of the upper member and the lowermember may be provided with an aperture or the like, with the otherbeing provided with a projection that snap-fits into the aperture sothat those fitting-in brings about a click feeling or issues a sound.Alternatively, configuration may be such that metal or resin in the formof a dome spring for example is deformed that is a circular plate havinga slightly downward convex curved surface so that e.g. when the circularplate is pressed at its center portion from above toward below, theupward convex curved surface is warped into a concave curved surface toproduce a sound or vibration at that time.

Ninth Embodiment

FIG. 21 shows an applicator 1000 of a ninth embodiment. The applicator1000 comprises a housing 1001 and a pressing mechanism 1015.

As shown in FIG. 22 , similarly to the above embodiments, the housing1001 comprises a peripheral base part 1002. The peripheral base part1002 has in its long-side-direction edges 1011 a notch 1012 in the shapeof a bracket for example. The peripheral base part 1002 has in itswidth-side edge 1013 a notch 1014 in the shape of an arch for example.Other than the above, the housing 1001 is substantially the same as thehousing 301 of the fourth embodiment. Accordingly, the housing 1001 willnot be again described. In the following description, parts of thehousing 1001 are appropriately designated at reference numerals of 900sthat are obtained by adding 600 to reference numerals imparted tocorresponding parts of the housing of the fourth embodiment.

The pressing mechanism 1015 generally comprises an upper structure 1016and a lower structure 1017. The upper structure 1016 comprises asubstantially inverted-U-shaped or substantially inverted-arch-shapedelastic expansion part 1018. The elastic expansion part 1018 is made ofe.g. a synthetic resin having an elasticity. Accordingly, when theelastic expansion part 1018 is subjected at its center portion to aforce from above, the elastic expansion part 1018 can deform such thatboth end portions 1019 thereof move outward apart from each other. Inthe embodiment, the both end portions 1019 of the elastic expansion part1018 are formed into a substantially cylindrical shape. In a free state,the interval between the left and right end portions 1019 is equal to orslightly greater than the distance between a pair of bracket-shapednotches 1012 formed in the long-side-direction edges 1011 of the housing1001.

The elastic extension part 1018 has at its center region a substantiallyquadrangular opening 1020 extending through a top surface and anundersurface thereof. The top surface of the elastic expansion part 1018includes a pair of grooves 1021 extending straight outward fromdiagonally confronting corners of the opening 1020 toward the both endportions 1019.

As shown in FIG. 23 , a torsion spring 1022 is stored in the opening1020 and the grooves 1021. The torsion spring 1022 includes a windingportion 1023 of a wound wire and a pair of arm portions 1024 extendingstraight from both ends of the winding portion 1023. The thus configuredtorsion spring 1022 is retained via a pin 1025 on the elastic expansionpart 1018, with the winding portion 1023 being stored in the opening1020, with the arm portions 1024 being stored in the grooves 1021. Thepin 1025 engages with the center undersurface of the elastic expansionpart 1018 so that the winding portion 1023 is retained in the opening1020, with the arms of the torsion spring 1022 being contracted from aposition indicated by a solid line in FIG. 23(b) to a position indicatedby a broken line, whereby the elastic expansion part 1018 is biased bythe arm portions 1024 such that its both end portions 1019 come closerto each other.

In the embodiment, the elastic expansion part 1018 has at itsundersurface center a groove 1026 extending in the width direction inorder to position the pin 1025, with the pin 1025 being stored in thegroove 1026.

A finger hold 1027 is assembled on the elastic expansion part 1018. Thefinger hold 1027 includes an upper portion 1028 against which the userpresses his/her finger (e.g. thumb) and a pair of legs 1029 extendingdownward from the undersurface of the upper portion 1028. Each of thelegs 1029 has at its lower end an engaging portion 1030. The thusconfigured finger hold 1027 is assembled on the elastic expansion part1018, with the winding portion 1023 of the torsion spring 1022 beingpositioned between the legs 1029, with the legs 1029 being inserted intothe opening 1020 from above to below.

The lower end engaging portions 1030 of the legs 1029 projectingdownward from the opening 1020 are engaged with and retained by acoupling member 1031. The coupling member 1031 is a substantiallycircular member and includes, at its top surface symmetrical locations,engaged portions 1032 of a shape corresponding to that of the lower endengaging portion 1030, with the lower end engaging portions 1030 of thelegs 1029 being inserted into the engaged portions 1032 so that thefinger hold 1027 is coupled to the coupling member 1031.

The lower structure 1017 includes, as shown in FIG. 24 , an upper member1033 and a lower member 1034. When viewed from above, the upper member1033 and the lower member 1034, particularly the lower member 1034 is ofa track shape substantially equal in size to a recess 910 of the housing1001. The undersurface of the upper member 1033 includes, at its bothends in the longitudinal direction, a platform 1035 projecting downward.The platforms 1035 have, at both end sides in the longitudinaldirection, their respective hook portions 1036 extending in the widthdirection, the hook portions 1036 each having at its center edge aprojection 1037 projecting downward. The upper member 1033 has acylindrical boss 1038 on the undersurface at the center. The cylindricalboss 1038 has at its lower end a diameter slightly larger than that ofthe other portions. The cylindrical boss 1038 includes a vertical crossgroove extending, in the long-side direction and the short-sidedirection of the upper member 1033, along the center axis upward fromthe lower end surface, whereby the lower end 1039 can deform so that itsouter diameter reduces when a force is applied from the periphery.

The lower member 103 generally comprises a center plate portion 1041 anda slant plate portion 1042 extending diagonally upward from both ends ofthe center plate portion 1041. The center plate portion 1041 has at itscenter a through-hole 1043 extending through the top surface andundersurface of the center plate portion 1041. The through-hole 1043 hason its inner surface at an upper end thereof an annular raised part(ridge) 1045. The inner diameter of the through-hole 1043 other than theannular raised part 1045 is substantially equal to the outer diameter ofthe cylindrical boss large-diameter lower end 1039, whereas the innerdiameter of the annular raised part 1045 is slightly smaller than theouter diameter of the cylindrical boss large-diameter lower end 1039.

Although not shown, the center plate portion 1041 may comprise aplurality of fan-shaped grooves arranged surrounding the through-hole1043 around the through-hole 1043. In this case, the cylindrical boss1038 need not have the vertical cross groove 1040.

The slant plate portions 1042 of the lower member 1034 have on its topsurface end sides engaging grooves 1047 corresponding in shape to thehook portions 1036 of the upper member 1033 so that, when the uppermember 1033 is mounted on the lower member 1034, the hook portions 1036of the upper member 1033 engage with the engaging grooves 1047 of thelower member 1034 to retain the lower member 1034.

Ends of the slant plate portion 1042 of the lower member 1034 has attheir respective centers longitudinal notches 1048 so that when theupper member 1033 is mounted on the lower member 1034, the projections1037 of the upper member 1033 engage with the notches 1048 of the lowermember 1034 to restrict the width-direction movement of the upper member1033 relative to the lower member 1034.

The thus configured pressing mechanism 1015 is assembled on the housing1001 as shown in FIGS. 21 to 23 . To be more specific, the lowerstructure 1017 is disposed in the center recess 910 of the housing 1001.The both end portions 1019 of the elastic expansion part 1018 of theupper structure 1016 is engaged with the longitudinal notches 1012 ofthe housing 1001 to retain the housing 1001 between these both endportions 1019. At this time, the user can assemble the upper structure1016 and the housing 1001 together while abutting his/her thumb andforefinger against the notches 1014 of the housing 1001 to hold thehousing.

Since the elastic expansion part 1018 is urged by the torsion spring1022 such that the both end portions 1019 thereof come closer to eachother, the housing 1001 is stably supported between the both endportions 1019. As shown, with the upper structure 1016 and the lowerstructure 1017 being assembled together, the undersurface of thecoupling member 1031 is in contact with the top surface of the fingerhold 1027, allowing the housing 1001 to be stably supported on thepressing mechanism 1015.

Upon attachment of the microneedle patch, as described above, theprotective sheet affixed to the bottom surface of the housing 1011 ispeeled off to expose the patch. The applicator 1000 is then placed onskin such that the peripheral base part of the housing 1011 abutsagainst skin. At this time, the both end portions 1019 of the elasticexpansion part 1018 are in contact with skin.

Subsequently, the pressing mechanism 1015 is pressed against skin whileabutting a finger (e.g. thumb) against the finger hold 1027 of thepressing mechanism 1015. This allows the both end portions 1019 of theelastic expansion part 1018 to be displaced outward in contact withskin, with its center portion being moved downward. In consequence, skinin the region confronting the microneedle patch is pulled in oppositedirections. Accordingly, skin is subjected to a tension so thatthereafter the microneedles easily stick into skin. Thus, skin isstretched out and resists against a pressure applied from a directionorthogonal to skin surface, resulting a state where a certain stress canbe produced. When microneedle tips are pressed against skin surface insuch a state, the microneedles can securely puncture skin surface.

Irregularities or grooves may be formed in the both end portions 1019 soas to increase the friction with skin or a pressure-sensitive adhesivemay be disposed thereon.

According as the finger hold 1027 advances toward skin, the lowerstructure 1017 deforms the housing 1011 while pressing a recess centerregion 913 of the housing 1011. When the deformation of the housing 1011proceeds, the slant plate portions 1042 of the lower member 103 arebrought into contact with the recess end regions, respectively, so thatthe microneedles supported on the recess center region are stronglypressed against skin.

When a force is applied to the finger hold 1027, the upper member 1033of the lower structure 1017 flexes at its center portion downward by apredetermined amount relative to the both side portions thereof; or thelower member 1034 flexes at its center portion upward by a predeterminedamount relative to the both side portions thereof; or the upper member1033 and the lower member 1034 flex at their center portions downwardand upward, respectively, by a predetermined amount, with the resultthat the cylindrical boss 1038 of the upper member 1033 enters thethrough-hole 1043 of the lower member 1034. Then, when a previouslydetermined given force is applied to the finger hold 1027, the lower end1039 of the cylindrical boss 1038 gets over the raised part 1045 of thelower member 1034 so that the lower end 1039 of the cylindrical boss1038 is engaged with the raised part (ridge) 1045 on the through-holeinner surface. The engagement of the lower end 1039 with the raised part1045 is sensed by the user via a feeling of the finger in contact withthe finger hold 1027 or via a sound. Therefore, the user can recognizethat a predetermined force has been applied to the finger hold 1027.Application of a predetermined force to the finger hold 1027 allows theneedles of the microneedle patch to enter into skin by a predeterminedamount. As a result, drug carried on the needles can securely beadministered to skin. In this manner, the cylindrical boss lower endportion 1039 and the raised part 1045 corresponding thereto act as anindicator that allows the user to sense that a predetermined force hasbeen applied to the finger hold 1027.

When the force applied to the finger hold 1027 is weakened to becomesmaller than the predetermined force, the lower end portion 1039 of thecylindrical boss 1038 is disengaged from the raised part (ridge) 1045 onthe through-hole inner surface due to the elastic recovery force of theupper member 1033 and the lower member 1034. The disengagement of thelower end portion 1039 from the raised part 1045 is sensed by the uservia the finger placed on the finger hold 1027. Thus, the user canrecognize that the predetermined force has not been persistently appliedto the finger hold 1027. By causing the user to recognize in advancethat the state where the lower end portion 1039 of the cylindrical boss1038 is engaged with the raised part (ridge) 1045 on the through-holeinner surface should be maintained for a predetermined period of time, arequired amount of drug can securely be administered to skin. Thispredetermined period of time may be described on instructions of theapplicator 1000 for example so that a predetermined amount of drug cansecurely be administered to skin.

When the force applied to the finger hold 1027 is released, the elasticexpansion part 1018 and the housing 1011 are restored to theirrespective pre-deformation shapes by their own elasticities.

The pressing mechanism 1015 and the housing 1001 may be engaged witheach other by the user before use. Alternatively, without being engaged,the both end portions 1019 of the elastic expansion part 1018 and thelongitudinal notches 1012 of the housing 1001 may be utilized or thepositions may visually be confirmed so that positioning on skin, etc. ismade in use.

Tenth Embodiment

FIGS. 25 ((a) and (b) of FIG. 25 ) shows an applicator 1100 of a tenthembodiment. In the applicator 1100, the coupling member 1031 of theupper structure 1016 in the pressing mechanism 1015 comprises a couplingstructure 1051 coupling the coupling member 1031 to the lower structure1017. In the embodiment, the coupling structure 1051 comprises a pair ofengaging hooks 1052 that are arranged symmetrically with respect to avertical center axis of the coupling member 1031. The interval betweenthe engaging hooks 1052 is designed to substantially equal to theshort-side direction width of the lower structure upper member 1033 inthe pressing mechanism so that the lower structure 1017 is retained inits entirety via the engaging hooks 1052 by the upper structure 1016.The other configurations are substantially the same as those of theninth embodiment. Hence, the same members or the same portions aredesignated at the same reference numerals and will not again bedescribed.

According to the applicator 1100 of the tenth embodiment configured inthis manner, with the upper structure 1016 and the lower structure 1017of the pressing mechanism 1015 being integrated, the pressing mechanism1015 can easily be assembled to the housing 1001.

Eleventh Embodiment

FIGS. 26 and 27 show an applicator 1200 of an eleventh embodiment. Theapplicator 1200 comprises a housing 1201 and a pressing mechanism 1215.

As shown in FIG. 27 , similarly to the ninth embodiment described above,the housing 1201 comprises a peripheral base part 1202. The peripheralbase part 1201 has long-side-direction edges 1211 each having a notch1212 in the shape of a bracket for example. Except for this, the housing1201 is substantially the same as the housing 301 of the fourthembodiment. Hence, detailed description of the housing 1201 will not berepeated. In the following description, parts of the housing 1201 areappropriately designated at reference numerals of 900s that are obtainedby adding 600 to reference numerals imparted to corresponding parts ofthe housing of the fourth embodiment.

The pressing mechanism 1015 generally comprises an upper structure 1216and a lower structure 1217. The upper structure 1216 comprises asubstantially inverted-U-shaped or substantially inverted-arch-shapedelastic expansion part 1218. The elastic expansion part 1218 is made ofe.g. a synthetic resin having an elasticity. Accordingly, when theelastic expansion part 1218 is subjected at its center portion to aforce from above, the elastic expansion part 1218 can deform such thatboth end portions 1219 thereof move outward apart from each other. Inthe embodiment, the both end portions 1219 of the elastic expansion part1218 are formed into a substantially cylindrical shape. In a free state,the interval between the left and right end portions 1219 is equal to orslightly greater than the distance between a pair of bracket-shapednotches 1212 formed in the long-side-direction edges 1211 of the housing1201.

The elastic extension part 1218 has at its center region a substantiallyquadrangular opening 1220 extending through a top surface and anundersurface thereof. The top surface of the elastic expansion part 1218includes a pair of grooves 1221 extending straight outward fromdiagonally confronting corners of the opening 1220 toward the both endportions 1219.

A torsion spring 1222 is stored in the opening 1220 and the grooves1221. The torsion spring 1222 includes a winding portion 1223 of a woundwire and a pair of arm portions 1224 extending straight from both endsof the winding portion 1223. The thus configured torsion spring 1222 isretained via a pin 1225 on the elastic expansion part 1218, with thewinding portion 1223 being stored in the opening 1220, with the armportions 1224 being stored in the grooves 1221. The pin 1225 engageswith the center undersurface of the elastic expansion part 1218 so thatthe winding portion 1223 is retained in the opening 1220 with the armopening angle of the torsion spring 1222 being reduced, whereby theelastic expansion part 1218 is biased by the arm portions 1224 such thatthe both end portions 1219 thereof come closer to each other.

In the embodiment, the elastic expansion part 1218 has at itsundersurface center a groove 1226 extending in the width direction inorder to position the pin 1225, with the pin 1225 being stored in thegroove 1226.

A finger hold 1227 is assembled on the elastic expansion part 1218. Thefinger hold 1227 includes an upper portion 1228 against which the userpresses his/her finger (e.g. thumb) and a pair of legs 1229 extendingdownward from the undersurface of the upper portion 1228. Each of thelegs 1229 has at its lower end an engaging portion 1230. The thusconfigured finger hold 1227 is assembled on the elastic expansion part1218, with the winding portion 1223 of the torsion spring 1222 beingclamped between the legs 1229, with the legs 1229 being inserted intothe opening 1220 from above to below.

The lower end engaging portions 1230 of the legs 1229 projectingdownward from the opening 1220 are engaged with and retained by acoupling member 1251. The coupling member 1251 is an inverted-pan-shapedmember (in the shape of a pan turned upside down) having a cylindricalwall 1252 with a vertical center axis and a ceiling wall 1252 coupled toan upper end of the cylindrical wall 1252. The ceiling wall 1253includes an axially symmetrical engaged portion 1254 that corresponds inshape to a finger hold lower end engaging portion 1230, with the fingerhold lower end engaging portion 1230 being fitted in and engaging withthe engaged portion 1254 so that the finger hold 1227 is coupled to thecoupling member 1251.

The ceiling portion 1253 has at its center aninverted-truncated-cone-shaped opening 1255 (in the shape whose diametergradually increases from the inner end toward the outer end). Theopening 1255 stores a deformation member 1256 that includes a circularplate portion and a dish-like thin metal plate obtained by shaping thecircumferential edge of the circular plate portion into aninverted-truncated cone. In order to retain the deformation member 1256in the opening 1255, the opening edge is of a shape corresponding to thecircumferential edge inverted-truncated-cone shape, as described above.

The circular plate portion of the deformation member 1256 has a slightlydownward convexly curved surface so that, for example, when the circularplate portion is pressed at its center portion from below toward above,the downward convexly curved surface warps into a concavely curvedsurface to produce a sound or a vibration at that time.

In order to retain the deformation member 1256 in the opening 255, aholding member 1257 is disposed on the deformation member 1256 and isfixed to the coupling member 1251. Fixing of the holding member 1257 tothe coupling member 1251 can be performed for example by engaging anengaging protrusion formed on the holding member 1257 with an engagedportion formed on the coupling member 1251 correspondingly to theengaging protrusion.

In order to retain an ascending/descending member 1261 that willhereinafter be described, the coupling member 1251 has, at locationsaxially symmetrical with respect to the ceiling wall 1253, a pair ofengagement holes 1257 extending through the top surface (outer surface)and the undersurface (inner surface).

The ascending/descending member 1261 is a pan-shaped member having acylindrical wall 1262 with a vertical center axis and a bottom wall 1263coupled to a lower end of the cylindrical wall 1262. The outer diameterof the ascending/descending member cylindrical wall 1262 is smaller thanthe inner diameter of the coupling member cylindrical wall 1252. Theascending/descending member collect wall 1262 has at its upper edge apair of engagement portion 1264 that is axially symmetrically formed,while the ascending/descending member bottom wall 1263 has at its topsurface center a pillar 1265 that extends upward.

For assembling, the thus configured ascending/descending member 1261stores a coil spring 1266 in the inside thereof, with theascending/descending member cylindrical wall 1262 being inserted intothe coupling member cylindrical wall 1253 from below, with theengagement portion 1264 being engaged such that it can rise and lowerthrough a groove or projection formed in the inner wall of the couplingmember 1251. The axial (longitudinal) length of the coil spring 1266 isdetermined such that, with the coupling member 1251 and theascending/descending member 1261 being assembled together, the coilspring 1266 is compressed between the ceiling wall 1253 and the bottomwall 1263 so that the ascending/descending member is urged toward andretained at a most lowered position (lowest position) with respect tothe coupling member 1251.

The length of the pillar 1265 of the ascending/descending member 1261 isdetermined such that, in the state where the ascending/descending member1261 lies at the lowest position with respect to the coupling member1251 by the coil spring 1266 with the coupling member 1251 theascending/descending member 1261 being combined together, the upper endof the pillar 1265 comes into light contact with or no contact with thecenter portion of the deformation member 1256.

The lower structure 1217 includes a quadrangular plate 1271 havingsubstantially the same size as that of the recess center region 913 ofthe housing 1201. The plate 1271 has on its top surface at a centerregion at least one projection, with engaging portions 1273 being formedon confronting edges lying on both sides of the projection 1272. Thethus configured plate 1271 is coupled to the ascending/descending member1261 while engaging the projection 1272 and the engaging portions 1273with a corresponding hole (not shown) formed in the ascending/descendingmember bottom wall 1263 and engaged portions 1274, respectively.

Upon attaching the microneedle patch, the protective sheet affixed tothe bottom surface of the housing 1211 is peeled off to expose thepatch. Since the protective seal has an easy peel function, it caneasily be peeled off. The applicator 1200 is then placed on skin suchthat the peripheral base part of the housing 1211 abuts against skin.

Alternatively, when attaching the microneedle patch, the protectivesheet affixed to the bottom surface of the housing 1211 is peeled off toexpose the patch. Due to having an easy peel function, the protectivesheet can easily be peeled off. The housing 1211 may then be coupled viathe lower structure 1217 to the upper structure 1216, and the applicator1200 may be placed on skin to abut the peripheral portion of the housing1211 against skin.

Otherwise, upon attachment of the microneedle patch, the housing 1211 iscoupled via the lower structure 1217 to the upper structure 1216, andthen the protective sheet affixed to the bottom surface of the housing1211 is peeled off to expose the patch. Afterword, the applicator 1200may be placed on skin, and the peripheral portion of the housing 1211may be abutted against skin.

Otherwise, the pressing mechanism 1215 may be engaged such that theplate 1271 of the lower structure 1217 is abutted against the recess 910of the housing 1201 and such that the both ends 1219 of the elasticexpansion part 1218 are positioned in the longitudinal notches 121 ofthe housing 1201.

In this state, the both end portions 1219 of the elastic expansion part1218 are in contact with skin.

Succeedingly, the pressing mechanism 1215 is pressed against skin whileabutting a finger (e.g. thumb) on the finger hold 1227 of the pressingmechanism 1215. This allows the both end portions 1219 of the elasticexpansion part 1218 to be displaced outward in contact with skin whileits center portion is moved downward. In consequence, skin in the regionconfronting the microneedle patch is pulled in opposite directions.Accordingly, skin is subjected to a tension so that thereafter themicroneedles easily stick into skin.

According as the finger hold 1227 advances toward skin, the lowerstructure 1217 deforms the housing 1211 while pressing the recess centerregion 913 of the housing 1211. When the deformation of the housing 1011proceeds, the microneedles supported on the recess center region arestrongly pressed against skin.

When a predetermined force is applied to the finger hold 1227, theascending/descending member 1261 ascends relative to the coupling member1251, and the pillar 1265 pushes the deformation member 1256 at itscenter portion or central peripheral portion from below. As a result,the deformation member 1256 deforms from a downward convex state to adownward concave state, to produce a shock and a sound. This shock issensed by the user through the finger placed on the finger hold 1227.Therefore, the user can recognize that a predetermined force has beenapplied to the finger hold 1227. Application of a predetermined force tothe finger hold 1227 allows the needles of the microneedle patch toenter into skin by a predetermined amount. As a result, drug carried onthe needles can securely be administered to skin. In this manner, thedeformation member 1256 acts as an indicator that allows the user tosense that a predetermined force has been applied to the finger hold1227.

When the force applied to the finger hold 1227 is weakened to becomesmaller than the predetermined force, the ascending/descending member1261 and the pillar 1265 thereof return to the descent positions by anurging force of the coil spring 1266. As a result, the deformationmember 1256 restores from the downward concave state to the downwardconvex state by its own elastic recovery force. Restoring of thedeformation member 1256 to the downward convex state is sensed via asound and a shock by the user through the finger placed on the fingerhold 1227. Thus, the user can recognize that the predetermined force hasnot been persistently applied to the finger hold 1227. By causing theuser to recognize in advance that the state of deformation of thedeformation member 1256 should be maintained for a predetermined periodof time, a required amount of drug can securely be administered to skin.This predetermined period of time may be described on instructions ofthe applicator 1200 for example so that a predetermined amount of drugcan securely be administered to skin.

Although in the above eleventh embodiment the plate 1271 of the lowerstructure 1217 is fitted to the undersurface of the ascending/descendingmember 1261 to deform the housing 1201 via this plate 1271, theascending/descending member 1261 may directly press the housing 1201 atthe recess center portion 913 to deform the housing 1201, as shown inFIGS. 28 and 29 .

The elastic expansion part 1218 of the pressing mechanism 1215 cancontrol the spreading force due to the elasticity of the elasticexpansion part itself and/or the resilience of the torsion spring, withthe result that the force to spread skin can be maintained constant.Although the microneedles can easily be inserted by spreading skin andapplying a tension, the state of skin differs at sites of skin ordepending on individuals. By keeping constant the force to spread skinusing this method, the differences based on the sites and individualscan be reduced so that the microneedles can be inserted into skin with ahigh accuracy.

Although in this specification the torsion spring has been exemplarilydescribed as means urging the elastic expansion part, the torsion springmay be replaced by an elastic body such as a coil spring or a rubber, ora foam body.

The applicator of this disclosure may hermetically be packaged by apackaging material such as an aluminum laminate pouch having excellentlight-shielding properties. The packaging container may hermeticallycontain agents such as a moisture absorbent and an oxygen absorbent forsuppressing degradation of the microneedles and of drug carried thereon.

EXPLANATIONS OF LETTERS OR NUMERALS

-   1 microneedle patch applicator-   11 housing-   12 peripheral base part-   13 raised part-   14 outer edge-   15 contour-   16 long-side-direction contour part-   17 short-side-direction contour part-   18 long-side-direction side wall-   19 short-side-direction side wall-   20 upper end of long-side-direction side wall-   21 upper end of short-side-direction side wall-   22 long-side-direction tilted top-surface portion-   23 short-side-direction tilted top-surface portion-   24 boundary/concavely bent part-   25 recess-   26 circumferential wall-   27 bottom-   28 easy-to-deform part-   29 center region-   30 end region-   31 finger hold-   32 upper member-   33 lower member-   34 support-   35 boss-   36 end region (slant surface)-   37 center region-   38 protuberance-   39 through-hole-   40 microneedle patch-   41 patch storage space-   42 patch support surface-   43 sheet substrate-   44 microneedle array-   45 substrate film-   46 pressure-sensitive adhesive layer-   47 release treatment layer (release layer)-   48 base layer-   49 needle-   50 double-sided tape-   55 protective sheet-   56 deformation preventing member-   1000 applicator-   1001 housing-   1011 long-side-direction edge-   1012 notch-   1013 short-side-direction edge-   1014-   1015 pressing mechanism-   1016 upper structure-   1017 lower structure-   1018 elastic expansion part-   1019 end portion-   1020 opening-   1021 groove-   1022 torsion spring-   1023 winding portion-   1024 arm portion-   1025 pin-   1026 groove-   1027 finger hold-   1028 upper portion-   1029 leg-   1030 engaging portion-   1031 coupling member-   1032 recess-   1033 upper member-   1034 lower member-   1035 platform-   1036 hook portion-   1037 projection-   1038 cylindrical boss-   1039 lower end-   1040 vertical groove-   1041 center plate portion-   1042 slant plate portion-   1043 through-hole-   1045 raised part (ridge)-   1046 engaging groove-   1047 notch-   1051 coupling structure-   1052 engaging hook-   1200 applicator-   1201 housing-   1211 long-side-direction edge-   1212 notch-   1215 pressing mechanism-   1216 upper structure-   1217 lower structure-   1218 elastic expansion part-   1219 end portion-   1220 opening-   1221 groove-   1222 torsion spring-   1223 winding portion-   1224 arm portion-   1225 pin-   1226 groove-   1227 finger hold-   1228 upper portion-   1229 leg-   1230 engaging portion-   1251 coupling member-   1252 cylindrical wall-   1253 ceiling wall-   1254 recess-   1255 opening-   1256 deformation member-   1257 engagement hole-   1261 ascending/descending member-   1262 cylindrical wall-   1263 bottom wall-   1264 engagement portion-   1265 pillar-   1266 coil spring-   1071 plate-   1272 projection-   1273 engaging portion

The invention claimed is:
 1. An apparatus for forcing an applicatorsupporting a microneedle patch to apply the microneedle patch onto askin, comprising: a substantially inverse arch-shaped or inverseU-shaped elastic member having a pair of end portions and a centralportion positioned between the pair of end portions, the central portionhaving a first opening extending through a top surface and a bottomsurface of the central portion; a finger hold having an upper portiononto which a user applies a pressure and a pair of leg portion extendingdownward from the upper portion, the finger hold being assembled withthe elastic member with the pair of leg portions extending through thefirst opening; a coupling member disposed below the first opening andcoupled to the finger hold through the pair of leg portions, anascending/descending member disposed under the coupling member andcoupled to the coupling member such that the ascending/descending membercan move upward and downward relative to the coupling member, and afirst spring disposed between the finger hold and the coupling member tobias the elastic member such that the end portions come closer to eachother.
 2. The apparatus of claim 1, wherein the first spring is atorsion spring.
 3. The apparatus of claim 1, wherein the first springcomprises a winding portion of a wound wire and a pair of arm portionsstraightly extending from opposite ends of the winding portion.
 4. Theapparatus of claim 3, wherein the finger hold is assembled with theelastic member with the winding portion of the first spring placedbetween the pair of leg portions and with the pair of leg portionspassed through from the top surface to the bottom surface of the firstopening.
 5. The apparatus of claim 1, wherein the first spring comprisesa pair of arms each extending from the central portion toward the pairof end portions of the elastic member, wherein the elastic membercomprises a pair of grooves extending from the central portion inopposite directions toward the end portions of the elastic member,wherein each of the pair of arms of the first spring is placed in eachof the pair of grooves.
 6. The apparatus of claim 1, comprising a secondspring disposed between the coupling member and the ascending/descendingmember and biasing the ascending/descending member into a lowermostposition relative to the coupling member.
 7. The apparatus of claim 6,wherein the second spring is a coil spring.
 8. The apparatus of claim 7,wherein the coupling member has a second opening extending through a topsurface and a bottom surface of the coupling member, the apparatusfurther comprising a deformable member having a downward-convex stateand a pillar extending toward the deformable member such that, when theascending/descending member is moved upward relative to the couplingmember against a biasing force from the second spring, the deformablemember deforms from the downward-convex state to an upward-convex stateto produce a sound.